RBSN p.Val762Leu

Variant names:

• chr3-15073853-C-A
• NM_022340.4:c.2284G>T
• RBSN p.Val762Leu

Your query was ambiguous. Multiple possible variants found:

• chr3-15073853-C-A
• chr3-15073853-C-G
• chr3-15073851-TAC-CAA
• chr3-15073851-TAC-AAG
• chr3-15073851-TAC-GAG
• chr3-15073851-TAC-CAG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022340.4(RBSN):​c.2284G>T​(p.Val762Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V762A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBSN NM_022340.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.90
• Publications: 0 publications found

Genes affected

RBSN (HGNC:20759): (rabenosyn, RAB effector) This gene encodes a protein that belongs to the FYVE zinc finger family of proteins. The encoded protein interacts with Ras-related proteins that regulate membrane trafficking. A missense mutation in this gene is associated with a defect in the early endocytic pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

RBSN Gene-Disease associations (from GenCC):

• congenital neutropenia-myelofibrosis-nephromegaly syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000289750 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022340.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBSN	NM_022340.4	MANE Select	c.2284G>T	p.Val762Leu	missense	Exon 14 of 14	NP_071735.2	Q9H1K0-1
	RBSN	NM_001302378.2		c.2284G>T	p.Val762Leu	missense	Exon 13 of 13	NP_001289307.1	Q9H1K0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBSN	ENST00000253699.7	TSL:1 MANE Select	c.2284G>T	p.Val762Leu	missense	Exon 14 of 14	ENSP00000253699.3	Q9H1K0-1
	RBSN	ENST00000945194.1		c.2374G>T	p.Val792Leu	missense	Exon 14 of 14	ENSP00000615253.1
	RBSN	ENST00000476527.7	TSL:2	c.2284G>T	p.Val762Leu	missense	Exon 13 of 13	ENSP00000422551.1	Q9H1K0-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.32	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.76
gMVP		0.22
Mutation Taster		=35/65	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-15115360;